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NCT Number: NCT04642430

COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation

Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Having a stroke can affect a patient's ability to speak, eat, walk, work, care for themselves, and interact with others. Not only can it ruin one's life, but it can also be fatal. A stroke occurs when blood flow to the brain is blocked by a clot, depriving brain cells of oxygen. In people with atrial fibrillation, blood flow is sluggish in the top chambers of the heart, and blood clots can form there. When a piece of a clot breaks off, it can travel to the brain and cause a stroke. That's where blood thinners come in. Blood thinners, or anticoagulants, decrease the chances of blood clots forming in the heart, reducing the risk of stroke. Studies show that blood thinners are highly effective at reducing the risk of stroke by up to 95%.

The conventional blood thinner is warfarin, taken by mouth. Warfarin requires regular blood tests to make sure a patient getting the correct dose. The patient also may have to avoid certain foods since the medication can interact with them. Newer blood thinners, known as direct-oral anticoagulants (DOACs) are available, which do not require regular blood tests and do not interact with foods. Two of the new blood thinners are called rivaroxaban and apixaban. Like warfarin, they can be taken by mouth, and studies have shown them to be as effective as warfarin.

Both rivaroxaban and apixaban have been approved for stroke prevention in AF by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF and patient values around bleeding highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.

The trial is to assess bleeding rates and superiority of using apixaban versus rivaroxaban in patients with non-valvular atrial fibrillation.

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Key information

Conditions

Atrial Fibrillation Arrhythmias, Cardiac Cardiovascular Diseases Heart Diseases Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Victoria Cardiac Arrhythmia Trials, Victoria, British Columbia, Canada

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About this study

Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Oral anticoagulants such as Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are highly effective at reducing the risk of stroke by up to 95%. Randomized controlled trials (RCTs) have compared apixaban and rivaroxaban (both DOACs) to VKAs for stroke prevention in AF, and are approved for this use by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF, patient values around bleeding, and litigation highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.

The objective of this RCT is to compare the safety of the first 12 months of apixaban twice daily to rivaroxaban once daily in patients with non-valvular AF (NVAF). Patients will be monitored for the primary outcome of clinically relevant bleeding (CRB; a composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events during follow-up. This trial will directly inform clinical practice and the choice of first-line therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 years old
  • Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines

Exclusion criteria

  • Creatinine clearance =<15 ml/min calculated using the Cockcroft-Gault formula
  • Any contraindication for anticoagulation with apixaban or rivaroxaban as determined by the treating physician such as, but not limited to:
  • active bleeding
  • history of mechanical valve
  • other indication for anticoagulation (e.g. mechanical valves, venous thrombosis)
  • dual antiplatelet agent use
  • known liver disease with coagulopathy
  • use of contraindicated medications (strong inducers/inhibitors of CYP 3A4/5, P-glycoprotein)
  • pregnancy or breastfeeding

Treatment and study plan

Apixaban

Drug

Refer to Apixaban group

Other names: Eliquis

Rivaroxaban

Drug

Refer to Rivaroxaban group

Other names: Xarelto

Primary outcomes

  1. The rate of adjudicated clinically relevant bleeding (CRB) events

    Time frame: For the duration of the study: 12 months

    CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events

Secondary outcomes

  1. Adjudicated Major Bleeding events

    Time frame: For the duration of the study: 12 months

    Major Bleeding includes clinically overt bleeding and is associated with:

    • Fatal bleeding, and/or
    • Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
    • A fall in hemoglobin of ≥20 g/L, or
    • Leading to transfusion of ≥2 units of whole blood or red cells.

  2. Adjudicated Clinically Relevant Non-Major Bleeding events

    Time frame: For the duration of the study: 12 months

    Clinically relevant non-major bleeding will be defined as:

    • Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria:
    • Requiring medical intervention by a healthcare professional
    • Leading to hospitalization or increased level of care
    • Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation

  3. Adjudicated stroke/TIA events

    Time frame: For the duration of the study: 12 months

    Stroke is defined as non-traumatic focal neurologic deficit lasting ≥ 24 hours and confirmed on cerebral imaging (computed tomography or magnetic resonance imaging).

    Transient ischemic attack (TIA) is defined as a temporary loss of blood flow to a part of the brain with focal neurologic deficit lasting < 24 hours without imaging evidence of acute infarction.

    Strokes are to be classified as ischemic, hemorrhagic stroke, or uncertain. Hemorrhagic strokes are considered and will be reported as both bleeding events as well as stroke endpoints. The location of the bleeding can be determined from the diagnostic imaging reports.

  4. All-cause mortality

    Time frame: For the duration of the study: 12 months

    Using a binary outcome of an event or no event (Individual rates of death, all causes).

  5. Medication adherence

    Time frame: For the duration of the study: 12 months

    Reported as the number of patients self-reporting "all assigned medications were taken" "missing at least one dose of study medication", or "not able to take all of the study medications" out of the total number of medication compliance assessments done respectively

  6. Incremental cost-effectiveness ratio

    Time frame: For the duration of the study: 12 months

    We will model the prognosis of a cohort of patients receiving rivaroxaban versus apixaban. The results will be presented as incremental cost per QALY gained, incremental costs per one clinically relevant bleeding cases prevented, and incremental cost per one life year saved.

Study contacts

Contact information is provided by the study sponsor or research team.

Erin Thomas

CONTACT

[email protected]

613-737-8899 ext. 79714

Lana Castellucci, MD, FRCPC

CONTACT

[email protected]

613-737-8899 ext. 74641

Sponsors and collaborators

Lead sponsor

Ottawa Hospital Research Institute

Other

Collaborators

  • Canadian Institutes of Health Research (CIHR)
  • Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Registry information

Acronym: COBRRA-AF

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Nov 24, 2020
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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